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Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?
No full textOutcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS ( = 0.04) and patients who required bowel resections had lower median OS ( = 0.009) compared to rest of the cohort.IMPACT STATEMENT Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently. This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time. These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours
Long term testosterone undecanoate replacement therapy: impact of ethnicity.
No full textBACKGROUND
Testosterone Replacement Therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety and efficacy profiles across different ethnicities for long term TRT remain unclear.
OBJECTIVE
To measure the impact of ethnicity on various biochemical parameters following Testosterone Undecanoate (TU) replacement.
METHOD
A retrospective analysis of 50 male patients treated with TU from 2006 to 2017 in a large secondary care centre was performed. Changes in total testosterone, PSA, haematocrit, haemoglobin, total cholesterol, low density lipoprotein (LDL) over eight years of treatment were analysed. Wilcoxon rank sum test was used to assess differences in these parameters between Caucasians and South Asians.
RESULTS
31 Caucasians (age: median (IQR) 55.0 years (49.0-68.0); total duration of follow up 6.1 years (2.9-9.3) and 19 South Asians (age: median (IQR) 52.0 years (38.0-69.0); duration of follow up 6.5 years (1.3-8.4) were treated with TU during the study period. There was no significant difference in total testosterone levels between the two ethnicities. We noted a higher free and bioavailable testosterone in South Asians compared to Caucasians, albeit within their reference range. PSA was higher in Caucasians compared to South Asians at two and eight years of TU therapy. After one year of TRT, haematocrit was higher in South Asians compared to Caucasians at one year, whereas LDL and total cholesterol were significantly higher in Caucasians than South Asians.
CONCLUSIONS
Caucasians have a tendency towards increased PSA, total cholesterol and LDL compared to South Asians with TU replacement therapy. There is a higher increment of haematocrit in South Asians following one year of TU replacement therapy. All biochemical changes following TRT were within the respective reference ranges suggesting no apparent risk of prostate cancer and venous thromboembolism
Low dose Btk inhibitors selectively block platelet activation by CLEC-2.
No full textInhibitors of the tyrosine kinase Btk have been proposed as novel antiplatelet agents. In this study we show that low concentrations of the Btk inhibitor ibrutinib block CLEC-2-mediated activation and tyrosine phosphorylation including Syk and PLCγ2 in human platelets. Activation is also blocked in patients with X-linked agammaglobulinaemia (XLA) caused by a deficiency or absence of Btk. In contrast, the response to GPVI is delayed in the presence of low concentrations of ibrutinib or in patients with XLA, and tyrosine phosphorylation of Syk is preserved. A similar set of results is seen with the second-generation inhibitor, acalabrutinib. The differential effect of Btk inhibition in CLEC-2 relative to GPVI signalling is explained by the positive feedback role involving Btk itself, as well as ADP and thromboxane A2 mediated activation of P2Y12 and TP receptors, respectively. This feedback role is not seen in mouse platelets and, consistent with this, CLEC-2-mediated activation is blocked by high but not by low concentrations of ibrutinib. Nevertheless, thrombosis was absent in 8 out of 13 mice treated with ibrutinib. These results show that Btk inhibitors selectively block activation of human platelets by CLEC-2 relative to GPVI suggesting that they can be used at 'low dose' in patients to target CLEC-2 in thrombo-inflammatory disease
Secondary care consultant clinicians' experiences of conducting emergency care and treatment planning conversations in England: an interview-based analysis.
No full textOBJECTIVE
To examine secondary care consultant clinicians' experiences of conducting conversations about treatment escalation with patients and their relatives, using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process.
DESIGN
Semi-structured interviews following ward round observations.
SETTING
Two National Health Service hospitals in England.
PARTICIPANTS
Fifteen medical and surgical consultants from 10 specialties, observed in 14 wards.
ANALYSIS
Interview transcripts were analysed using thematic analysis.
RESULTS
Three themes were developed: (1) determining when and with whom to conduct a ReSPECT conversation; (2) framing the ReSPECT conversation to manage emotions and relationships and (3) reaching ReSPECT decisions. The results showed that when timing ReSPECT conversations, consultant clinicians rely on their predictions of a patient's short-term prognosis; when framing ReSPECT conversations, consultant clinicians seek to minimise distress and maximise rapport and when involving a patient or a patient's relatives in decision-making discussions, consultant clinicians are guided by their level of certainty about the patient's illness trajectory.
CONCLUSIONS
The management of uncertainty about prognoses and about patients' emotional reactions is central to secondary care consultant clinicians' experiences of timing and conducting ReSPECT conversations
Management of venous thromboembolism in patients experiencing direct oral anticoagulant treatment failure: a single-center review of practice and outcomes.
No full textDirect oral anticoagulants (DOACs) have gained in popularity over vitamin K antagonists for the treatment of venous thromboembolism, however their efficacy is not routinely monitored. It is therefore a clinical challenge to know how to respond when treatment with DOACs fails, and there is little formal guidance on how to manage these patients. We sought to characterize VTE patients who experienced DOAC failure at our institution, and rationalize subsequent treatment strategies. We collated the details of 54 consecutive patients with suboptimal response or breakthrough thrombosis on a DOAC, from our large specialist-led thrombosis clinic. Initial treatment changes were recorded, as well as long-term anticoagulation therapy and treatment outcomes. On first recognition of DOAC failure, 69% of patients were temporarily switched to therapeutic-dose low molecular weight heparin; most of the remaining patients were treated with an alternative DOAC regimen. After a limited period of parenteral treatment, 84% of patients returned to oral anticoagulation, the majority of whom experienced no further treatment failures. By the end of follow-up, 72% of patients were either on long-term DOAC therapy or had completed treatment altogether. In the absence of evidence or guidelines, brief rescue of anticoagulation with parenteral therapy can be an effective strategy when treatment with a DOAC fails
Equal rights in autoimmunity: is Sjögren's syndrome ever 'secondary'?
No full textSjögren's syndrome (SjS) accompanied by other systemic autoimmune rheumatic connective tissue diseases has historically been termed 'secondary' in contrast to 'primary' SjS as a standalone entity. However, it is a matter of a long-standing debate whether the prefixes 'primary' and 'secondary', including a temporal component, are obsolete in the terminology of SjS. We review the history and the pathophysiological, chronological, genetic, histological and clinical data underlying the concept of 'secondary' SjS. There are important unintended consequences of the nomenclature; notably 'secondary' SjS has been much less researched and is often excluded from clinical trials. We argue for further research, a change in terminology and more stringent classification. Further we highlight possible opportunities for trials in SjS and other systemic autoimmune diseases that might contribute to an advance in care for all patients with SjS
Nonsteroidal anti-inflammatory drugs and incidence of atrial fibrillation: a meta-analysis.
No full textBACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for many inflammatory disorders and pain-related illnesses. Despite their widespread use, the association between NSAIDs and the incidence of atrial fibrillation (AF) remains unclear. The aim of this systematic review and meta-analysis is to investigate this association.
METHODS
A systematic review was conducted in MEDLINE, EMBASE and Cochrane databases from inception through August 2019 to identify studies that evaluated the risk of AF among patients using NSAIDs. Pooled risk ratios (RRs) and 95% CI were calculated using a random-effect, generic inverse variance method. The protocol for this meta-analysis is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42019141609).
RESULTS
Eight observational studies (four case-control studies and four cohort studies) with a total of 14 806 420 patients were enrolled. When compared with nonNSAIDs users, the pooled RR of AF in patients with NSAIDs use was 1.29 (95% CI 1.19-1.39). Meta-analyses based on the type of study were additionally performed. Subgroup analysis by study design revealed a significant association between the use of NSAIDs and AF for both case-control studies (pooled RR 1.37; 95% CI, 1.15-1.63) and cohort studies (pooled RR 1.22; 95% CI, 1.14-1.31). Sub-analyses based on specific NSAIDs showed pooled RRs of AF in patients using ibuprofen of 1.30 (95% CI 1.22-1.39), naproxen of 1.44 (95% CI 1.18-1.76) and diclofenac of 1.37 (95% CI 1.10-1.71), respectively. Funnel plot and Egger's regression asymmetry tests were performed and showed no publication bias.
CONCLUSION
NSAID use is associated with incident AF. Our study also demonstrated a consistent result among different NSAIDs
Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.
No full textPURPOSE
Our purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT).
METHODS AND MATERIALS
Our study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included from the start of UK IMRT guidance from February 2013 to October 31, 2017. Collected data included baseline demographics, treatment details, tumor control, sites of relapse, and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R.
RESULTS
The medical records of 385 consecutive patients were analyzed. Median follow-up was 24.0 months. Within 6 months of completing CRT, 86.7% of patients achieved a complete response. Three-year disease-free survival and overall survival were 75.6% and 85.6%, respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were 2 isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage, and failure to complete radiation therapy as planned.
CONCLUSIONS
The treatment results compare favorably to published outcomes from similar cohorts using 3-dimensional conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose as sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation of strategies to optimize CR should remain a priority in ASCC because the site of primary disease remains the overwhelming site of relapse